Functionalized ZIF‐90 for Gene‐mediated Chemotherapy to Ameliorate Multidrug Resistance in Breast Cancer Therapy

Abstract

Breast cancer, the most common cancer, is a threat to women's health. A great challenge for breast cancer is the multidrug resistance (MDR) problem. P‐glycoprotein (P‐gp) is one of main reasons to induce MDR in the therapy of breast cancer. A novel nanosystem based on ZIF‐90 was developed for alleviating MDR and to improve the therapeutic efficacy. In this investigation, ZIF‐90 was used as a carrier to deliver two kinds of DNA molecular beacons (MBs) and Doxorubicin (Dox). The loop sequences of two kinds of MBs were designed to specifically hybridize with the mRNAs related to P‐gp (MDR1 gene and ETS1 gene, respectively), thereby directly inhibiting the expression of downstream proteins P‐gp. The results of confocal fluorescence imaging and qRT‐PCR analysis indicated that MB and Dox were delivered into cells and the mRNAs related to P‐gp were silenced. The MTT assay showed that the IC50 of nanosystem to the drug‐resistant breast cancer cells (34.78 μg/mL) was much lower than the IC50 of Dox to the same cells (152.7 μg/mL). These results distinctly confirmed that the problem of MDR has been ameliorated by our designed nanosystem. It is our hope that this investigation may provide a new treatment strategy for enhancing the therapeutic efficacy of chemotherapy for breast cancer.

Metal‐Organic Frameworks Nanocarriers for Functional Nucleic Acid Delivery in Biomedical Applications

“…[38] Previously, two antisense nucleic acids were brought into MCF-7/ADM cells by a ZIF-90 nanodelivery system in our laboratory, which were simultaneously silenced with the drug resistance related multidrug resistance protein 1 (MDR1) gene and erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene. [39] Notably, the IC 50 value of (MB1 + MB2)/Dox@ZIF-90 was more than four times lower than that of DOX alone, indicating that the nanodelivery system could effectively reverse the multidrug resistance of MCF-7/ADM. In addition, our laboratory investigate the effect of the novel drug loading system to capture intracellular oncogenic miR-21 and miR-155 on MDA-MB-231 cell proliferation and migration, and the silencing effect of miRNAs was explored at the molecular level, which was proved to have the effect of adjuvant treatment of triple negative breast cancer.…”

“…ASO is a single stranded oligonucleotide, which after entering cells bind to their complementary target mRNA through the principle of base complementary pairing and then under the action of ribonuclease H1, inhibiting the expression of target genes [38] . Previously, two antisense nucleic acids were brought into MCF‐7/ADM cells by a ZIF‐90 nanodelivery system in our laboratory, which were simultaneously silenced with the drug resistance related multidrug resistance protein 1 (MDR1) gene and erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene [39] . Notably, the IC 50 value of (MB1+MB2)/Dox@ZIF‐90 was more than four times lower than that of DOX alone, indicating that the nanodelivery system could effectively reverse the multidrug resistance of MCF‐7/ADM.…”